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African-American coal mine inspector Ralph Burton (Harry Belafonte) becomes trapped underground in a cave-in while inspecting a mine in Pennsylvania. He can hear rescuers digging towards him, but after a few days they slow down and then stop completely. Alarmed, he digs his own way out. Reaching the surface, he finds a deserted world. (No bodies are seen at any time in the film.) Some discarded newspapers provide an explanation: one proclaims "UN Retaliates For Use Of Atomic Poison", another that "Millions Flee From Cities! End Of The World". Ralph later plays tapes at a radio station that an unknown nation had used radioactive isotopes as a weapon, yielding a dust cloud that spread globally and was completely lethal for a five-day period.

Travelling to New York City in search of other survivors, he finds the city vacant. Ralph busies himself restoring power to a building where he takes up residence. Just as the loneliness starts to become intolerable, he encounters a second survivor: Sarah Crandall (Inger Stevens), a white woman in her twenties. The two become fast friends, but Ralph grows distant when it becomes clear that Sarah is developing stronger feelings for him. Despite living in a post-apocalyptic world and despite the fact that Sarah seems unconcerned with their racial difference, Ralph cannot overcome the inhibitions instilled in him in a racist American society.

Ralph regularly broadcasts on the radio, hoping to contact other people. Eventually, he receives a signal from Europe, indicating there are at least a few other survivors. Things become vastly more complicated when an ill, white Benson Thacker (Mel Ferrer) arrives by boat. Ralph and Sarah nurse him back to health, but once he recovers, Ben sets his sights on Sarah and sees Ralph as a rival. Ralph is torn by conflicting emotions. He avoids Sarah as much as possible, to give Ben every opportunity to win her affections, but cannot quite bring himself to leave the city.

Ben finally grows tired of the whole situation, realizing he stands little chance with Sarah as long as Ralph remains nearby. He warns Ralph that the next time he sees him, he will try to kill him. The two armed men hunt each other through the empty streets. Finally, Ralph passes by the United Nations headquarters, climbs the steps in Ralph Bunche Park, and reads the inscription "They shall beat their swords into plowshares. And their spears into pruning hooks. Nation shall not lift up sword against nation. Neither shall they learn war any more", from the Book of Isaiah 2:4. He throws down his rifle and goes unarmed to confront Ben, who in turn finds himself unable to shoot his foe. Defeated, he starts walking away. Sarah appears. When Ralph starts to turn away from her, she makes him take her hand; then she calls to Ben and gives him her other hand. Together, the three walk down the street to build a new future together. The film ends not with "The End" but with "The Beginning".